中药新药与临床药理2026，Vol.37Issue(5)：807-816,10.DOI:10.19378/j.issn.1003-9783.2026.05.004
仙鹤草通过SIRT1/FOXO3A信号通路调控线粒体自噬对小鼠心肌纤维化的作用及机制
Effect and Mechanism of Agrimoniae Herba in Myocardial Fibrosis Mice by Regulating Mitophagy via the SIRT1/FOXO3A Signaling Pathway
摘要
Abstract
Objective To investigate the effect and mechanism of Agrimoniae Herba on myocardial fibrosis(MF)in mice based on the regulation of mitophagy via the silent information regulator 1(SIRT1)/forkhead box protein O3A(FOXO3A)signaling pathway.Methods Male Kunming mice were randomly divided into a normal group,model group,propranolol group(40 mg·kg-1),and low-,medium-,and high-dose Agrimoniae Herba groups(0.78,1.56,3.12 g·kg-1 crude drug),with 10 mice in each group.The MF mouse model was established by subcutaneous injection of isoproterenol(ISO,15 mg·kg-1)for 14 days.Concurrent with modeling,each administration group received the corresponding drugs by gavage(administration volume of 10 mL·kg-1)once daily for 14 consecutive days.Cardiac function was assessed using echocardiography,recording parameters including left ventricular ejection fraction(EF),left ventricular fractional shortening(FS),left ventricular end-systolic diameter(LVESD),and left ventricular end-diastolic diameter(LVEDD).Serum levels of cardiac enzymes[creatine kinase(CK),creatine kinase isoenzyme MB(CK-MB),lactate dehydrogenase(LDH)]and collagen metabolites[procollagen type Ⅰ C-terminal propeptide(PICP),type I collagen carboxy-terminal telopeptide(ICTP)]were measured using biochemical methods and ELISA.Histopathological morphology and collagen deposition in cardiac tissue were observed using HE and Sirius red staining.Mitochondrial membrane potential in cardiomyocytes was detected by flow cytometry.The expression of SIRT1/FOXO3A signaling pathway and autophagy-related proteins in cardiac tissue was assessed using immunofluorescence,immunohistochemistry,and Western Blot.Results Compared with the normal group,the model group showed significantly decreased EF and FS(P＜0.01),and significantly increased LVESD and LVEDD(P＜0.01);serum levels or activities of CK,CK-MB,LDH,ICTP,and PICP were significantly elevated(P＜0.01);myocardial fibers were disrupted with some inflammatory cell infiltration,and collagen deposition was significantly increased(P＜0.01);mitochondrial membrane potential in cardiomyocytes was significantly reduced(P＜0.01);the co-localization expression of LC3B and COXIV proteins in cardiac tissue was significantly increased(P＜0.01);the nuclear expression of FOXO3A in cardiac tissue was increased,and the protein expression of SIRT1,FOXO3A,BNIP3,LC3B,Beclin1,collagenⅠ,and collagen Ⅲ was significantly upregulated(P＜0.01),while p62 protein expression was significantly downregulated(P＜0.01).Compared with the model group,each Agrimoniae Herba dose group exhibited significantly increased EF and FS(P＜0.01),and significantly decreased LVESD and LVEDD(P＜0.01);serum levels or activities of CK,CK-MB,LDH,ICTP,and PICP were significantly reduced(P＜0.01);myocardial fibrosis was ameliorated,inflammatory cell infiltration was notably reduced,and collagen deposition was significantly decreased(P＜0.01);the co-localization expression of LC3B and COXIV proteins in cardiac tissue was significantly weakened(P＜0.05,P＜0.01);the nuclear expression of FOXO3A in cardiac tissue was reduced,and the protein expression of SIRT1,FOXO3A,BNIP3,LC3B,Beclin1,collagen Ⅰ,and collagen Ⅲ was significantly downregulated(P＜0.05,P＜0.01).Compared with the model group,the medium-and high-dose Agrimoniae Herba groups showed significantly upregulated p62 protein expression in cardiac tissue(P＜0.05,P＜0.01)and significantly increased mitochondrial membrane potential in cardiomyocytes(P＜0.05,P＜0.01).Conclusion Agrimoniae Herba can improve cardiac function and myocardial injury,reduce myocardial collagen deposition,and ameliorate fibrosis in MF mice.Its mechanism of action may be related to inhibiting the SIRT1/FOXO3A signaling pathway and regulating mitophagy.关键词
仙鹤草/心肌纤维化/SIRT1/FOXO3A信号通路/线粒体自噬/小鼠Key words
Agrimoniae Herba/myocardial fibrosis/SIRT1/FOXO3A signaling pathway/mitophagy/mice分类
医药卫生引用本文复制引用
安嘉琪,陈健,魏智祥,高星星,董志阔,张睦清,张一昕..仙鹤草通过SIRT1/FOXO3A信号通路调控线粒体自噬对小鼠心肌纤维化的作用及机制[J].中药新药与临床药理,2026,37(5):807-816,10.基金项目
国家自然科学基金项目(82505547) （82505547）
河北省中医药管理局科研计划项目(2021051). （2021051）
